MLPA: A Multi-scale Digital Twin Framework for Personalized Cancer Simulation and Treatment Optimization

Jake Y. Chen, James C Gu
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Abstract

We introduce the Multi-level Parameterized Automata (MLPA), an innovative digital twin model that revolutionizes personalized cancer growth simulation and treatment optimization. MLPA integrates macroscopic electronic health records and microscopic genomic data, employing stochastic cellular automata to model tumor progression and treatment efficacy dynamically. This multi-scale approach enables MLPA to simulate complex cancer behaviors, including metastasis and pharmacological responses, with remarkable precision. Our validation using bioluminescent imaging from mice demonstrates MLPA's exceptional predictive power, achieving an improvement in accuracy over baseline models for tumor growth prediction. The model accurately captures tumors' characteristic S-shaped growth curve and shows high fidelity in simulating various scenarios, from natural progression to aggressive growth and drug treatment responses. MLPA's ability to simulate drug effects through gene pathway perturbation, validated through equivalence testing, underscores its potential as a powerful tool for precision oncology. The framework offers a robust platform for exploring personalized treatment strategies, potentially transforming patient outcomes by optimizing therapy based on individual biological profiles. We present the theoretical foundation, implementation, and validation of MLPA, highlighting its capacity to advance the field of computational oncology and foster more effective, tailored cancer treatment solutions. As we progress towards precision medicine, MLPA stands at the forefront, offering new possibilities in cancer modeling and treatment optimization. The code and imaging dataset used is available at https://github.com/alphamind-club/MLPA.
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MLPA:用于个性化癌症模拟和治疗优化的多尺度数字双胞胎框架
我们介绍了多级参数化自动机(MLPA),这是一种创新的数字孪生模型,可彻底改变个性化癌症生长模拟和治疗优化。MLPA 整合了宏观电子健康记录和微观基因组数据,采用随机细胞自动机对肿瘤进展和治疗效果进行动态建模。这种多尺度方法使 MLPA 能够非常精确地模拟复杂的癌症行为,包括转移和药理反应。我们利用小鼠的生物发光成像进行了验证,证明了 MLPA 的卓越预测能力,在肿瘤生长预测方面比基线模型的准确性有所提高。该模型准确捕捉了肿瘤特征性的 S 型生长曲线,并在模拟各种情况(从自然进展到侵袭性生长和药物治疗反应)时表现出很高的保真度。通过等效性测试验证,MLPA 能够通过基因通路扰动来模拟药物效应,这突显了它作为精准肿瘤学强大工具的潜力。该框架为探索个性化治疗策略提供了一个强大的平台,通过根据个体生物特征优化治疗,有可能改变患者的预后。我们介绍了 MLPA 的理论基础、实施和验证,强调了它在推动计算肿瘤学领域发展和促进更有效、量身定制的癌症治疗方案方面的能力。随着我们向精准医学迈进,MLPA 站在了最前沿,为癌症建模和治疗优化提供了新的可能性。使用的代码和成像数据集可在 https://github.com/alphamind-club/MLPA 上获取。
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